Bariatric Metabolic Surgery vs Glucagon-Like Peptide-1 Receptor Agonists and Mortality

Key Points Question How are bariatric metabolic surgery (BMS) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) associated with mortality and major adverse cardiovascular events (MACEs) among patients with obesity and diabetes? Findings In this cohort study comprising 6070 patients, among individuals with a diabetes duration of 10 years or less, BMS was associated with a 62% reduction in mortality compared with GLP-1RAs, with weight reduction mediating the association. No difference was observed in the risk of mortality among those with a longer duration of diabetes, nor in the risk of MACEs among all patients. Meaning This study suggests that BMS was associated with greater reduced mortality compared with GLP-1RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss.


eMethods. Baseline Measurements
This observational, retrospective cohort study was based on data obtained from the electronic medical records of Clalit Health Services (Clalit).Clalit is the largest healthcare organization in Israel (country with mandatory universal health insurance for all citizens), providing care to 52% of the population (~4.8 million individuals).
Different from other countries such as the United States, Clalit is both an insurer and a provider of health services.Clalit's information systems are fully digitized and contribute to a centralized data warehouse containing both administrative and clinical data.
The following variables were extracted as of the index date: sociodemographic variables including patient sex, age (years), ethnicity (Jewish/non-Jewish/unknown), socioeconomic status (SES; low, medium, high), immigration status (born in Israel, immigrated to Israel), and peripherality (1-10, from residence in the periphery to the center area).The Peripherality Index is based on the Israeli Central Bureau for Statistics' Peripherality Index of Local Authorities, which categorizes local authorities in Israel by their proximity to the central economic hub.It considers potential accessibility, which includes proximity to other local authorities and population size, as well as proximity to the Tel Aviv District. 1 Diagnoses of co-morbidities, including atrial fibrillation, hyperlipidemia, and hypertension, were defined based on any documentation prior to the index date.Laboratory data were assessed based on any documentation in the community setting.These data included HbA1c concentration; blood levels of fasting plasma glucose (mg/dL), total cholesterol (mg/dL), HDL cholesterol (mg/dL), LDL cholesterol (mg/dL), and triglycerides (mg/dL); systolic and diastolic blood pressure (mmHg); BMI (kg/m 2 ); and smoking status (former, current, or non-smoker).Pharmaceutical treatments (yes/no for each treatment) were assessed based on ≥1 filled prescription during the year before the index date.These treatments included beta blocking agents, calcium channel blockers, agents acting on the renin-angiotensin system, lipid modifying agents, insulins, non-insulin injectable therapy, blood glucose lowering drugs, antidepressants, medications for weight reduction, and Sodium Glucose co-Transporter 2 (SGLT-2) Inhibitors.

eResults. Results of Sensitivity Analysis
A sensitivity analysis was conducted for the primary outcome (mortality), while excluding from the analysis individuals with a cancer diagnosis in the first two years of follow-up, yielded results consistent with those of the main analysis, (adjusted HR: 0.33, 95% CI: 0.21-0.52).The association was preserved when the percentages of the maximal change in HbA1c concentration during follow up was included in the model (HR: 0.36, 95%CI: 0.22-0.58),but disappeared once the percentages of the maximal change in BMI level was also introduced into the model (HR: 0.58, 95%CI: 0.32-1.03)(eTable).The models were adjusted for the following variables as of the index date: diabetes duration (months), age (years), ethnicity (Arabs, Jews), BMI (kg/m 2 ), HbA1c concentration, socioeconomic status, diagnosis of atrial fibrillation, diagnosis of hyperlipidemia, diagnosis of hypertension, smoking status (non-smoker, former, current, unknown), and using agents acting on the renin-angiotensin system, lipid modifying agents, insulin, SGLT-2 inhibitors, and other blood glucose-lowering drugs.No multicollinearity was observed between variables included in the analysis (VIFs<1.3).The models met the proportional hazards assumption.

eFigure.
Selection of Patients Who Underwent BMS, and Matching to Patients Treated With GLP-1RAs Associations Between Treatment Type (BMS/GLP-1RA) and Mortality According to the Duration of Diabetes, Excluding Individuals With a Cancer Diagnosis in the First Two Years of Follow-Up eTable.